title: MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies.
abstract: OBJECTIVE
  To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy.
  
  
  METHODS
  Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, β-amyloid, and α-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala.
  
  
  RESULTS
  pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and β-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions.
  
  
  CONCLUSIONS
  Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.
authors.affiliation: From the Department of Neuroscience (M.E.M., A.M.L., B.N.D., D.W.D.), Psychiatry and Psychology (T.J.F.), and Neurology (N.R.G.-R.), Mayo Clinic, Jacksonville, FL; and Department of Neurology (B.F.B., D.S.K., M.H.S., R.C.P.), Biomedical Statistics (S.A.P., T.G.L.), Radiology (M.L.S., J.L.G., G.M.P., P.V., C.R.J., K.K.), Nuclear Medicine (V.J.L.), Psychology (G.E.S.), Laboratory Medicine and Pathology (J.E.P.), and Center for Sleep Medicine (M.H.S.), Mayo Clinic, Rochester, MN.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Murray
authors.forename: Tanis J
authors.initials: TJ
authors.lastname: Ferman
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: Scott A
authors.initials: SA
authors.lastname: Przybelski
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Lesnick
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Liesinger
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Preboske
authors.forename: Val J
authors.initials: VJ
authors.lastname: Lowe
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Dugger
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Smith
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.forename: Michael H
authors.initials: MH
authors.lastname: Silber
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Kejal
authors.initials: K
authors.lastname: Kantarci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001344:Autopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020961:Lewy Body Disease / Q000150:complications*; D016013:Likelihood Functions; D008279:Magnetic Resonance Imaging; D008297:Male; D020187:REM Sleep Behavior Disorder / Q000209:etiology* / Q000473:pathology*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins